Breast Angiosarcoma Surveillance Study: UK national audit of management and outcomes of angiosarcoma of the breast and chest wall.

BACKGROUND: Breast angiosarcomas are rare tumours of vascular origin. Secondary angiosarcoma occurs following radiotherapy for breast cancer. Angiosarcomas have high recurrence and poor survival rates. This is concerning owing to the increasing use of adjuvant radiotherapy for the treatment of invasive breast cancer and ductal cancer in situ (DCIS), which could explain the rising incidence of angiosarcoma. Outcome data are limited and provide a poor evidence base for treatment. This paper presents a national, trainee-led, retrospective, multicentre study of a large angiosarcoma cohort. METHODS: Data for patients with a diagnosis of breast/chest wall angiosarcoma between 2000 and 2015 were collected retrospectively from 15 centres. RESULTS: The cohort included 183 patients with 34 primary and 149 secondary angiosarcomas. Median latency from breast cancer to secondary angiosarcoma was 6 years. Only 78.9 per cent of patients were discussed at a sarcoma multidisciplinary team meeting. Rates of recurrence were high with 14 of 28 (50 per cent ) recurrences in patients with primary and 80 of 124 (64.5 per cent ) in those with secondary angiosarcoma at 5 years. Many patients had multiple recurrences: total of 94 recurrences in 162 patients (58.0 per cent). Median survival was 5 (range 0-16) years for patients with primary and 5 (0-15) years for those with secondary angiosarcoma. Development of secondary angiosarcoma had a negative impact on predicted breast cancer survival, with a median 10-year PREDICT prognostic rate of 69.6 per cent, compared with 54.0 per cent in the observed cohort. CONCLUSION: A detrimental impact of secondary angiosarcoma on breast cancer survival has been demonstrated. Although not statistically significant, almost all excess deaths were attributable to angiosarcoma. The increased use of adjuvant radiotherapy to treat low-risk breast cancer and DCIS is a cause for concern and warrants further study.

Quinidine as a resistance modulator of epirubicin in advanced breast cancer: mature results of a placebo-controlled randomized trial.

PURPOSE: To evaluate the effect of quinidine, a putative modulator of P-glycoprotein-mediated drug resistance, on the response rate and toxicity profile of epirubicin in patients with advanced breast cancer. PATIENTS AND METHODS: Between 1989 and 1992, 223 eligible patients were randomized in double-blind fashion to receive epirubicin 100 mg/m2 by intravenous (i.v.) bolus and prednisolone 25 mg orally twice daily, along with either placebo or quinidine (250 mg) capsules, taken for 4 days before and 2 days after chemotherapy. Treatment was continued for a maximum of eight courses. RESULTS: Ten eligible patients did not complete the first cycle of treatment. Of the remaining patients, 106 in the placebo arm received 619 courses of treatment, and 107 in the quinidine arm received 612 courses. The median cumulative dose of epirubicin in both arms was 600 mg/m2. The median quinidine level (measured before epirubicin administration in 288 courses) was 5.5 mumol/L; at this concentration, the drug partially reverses anthracycline resistance in multidrug-resistant (MDR) breast carcinoma cells in vitro. There were no statistically significant differences in hematologic or gastrointestinal toxicity between the two arms. The response rate in the placebo arm was 44% (6% complete remission [CR], 38% partial remission [PR]), and in the quinidine arm was 43% (4% CR, 39% PR). Surviving patients have been monitored for a median time of 74 weeks, and there is no significant difference in the overall or progression-free survival between the two arms. The median survival times were 59 weeks for placebo and 47 weeks for quinidine patients. The estimated relative death rate (quinidine/placebo) was 1.2 (P = .247; 95% confidence interval [CI], 0.88 to 1.63). CONCLUSION: Quinidine at this dose does not significantly alter the toxicity profile, response rate, or survival after epirubicin chemotherapy in patients with advanced breast cancer. This may be due to ineffective modulation of P-glycoprotein by quinidine or the lack of expression of mdr-1 in a sufficient proportion of cells in these tumors, or alternative mechanisms underlying resistance to epirubicin.

The eye in acute leukaemia. 2. The management of solitary anterior chamber relapse.

Solitary relapse of acute lymphoblastic leukaemia (ALL) was diagnosed in the anterior chamber of the eye in five children. In all these cases, pathological confirmation of the diagnosis was obtained and there was no other evidence of relapse including cerebrospinal fluid (CSF) and bone marrow examinations. Each child had one adverse prognostic sign at the initial presentation (high white blood cell count, age or sex). Relapse always occurred soon after completion of maintenance chemotherapy (between one and 4 months), supporting the hypothesis that the eye is a pharmacological sanctuary to cytotoxic chemotherapeutic drugs. Radiotherapy to the involved orbit was given with an immediate response in all patients. The details of this treatment are discussed. Four of the five patients later relapsed, one locally and three in bone marrow; the prognosis of solitary ocular relapse therefore appears grave.

The eye in acute leukaemia. 1. Dosimetric analysis in cranial radiation prophylaxis.

The dose to the ocular lens during standard cranial irradiation prophylaxis in childhood acute lymphoblastic leukaemia (ALL) has been studied both in patients and in an anthropomorphic phantom. Doses to the lens depend on patient set-up and in order that this is minimised, a simple immobilisation technique is recommended. Surface thermoluminescent dosimeter (TLD) measurements seriously underestimate the dose received by the ocular lens. Previous measurements made in a phantom have used a large volume ionisation chamber and therefore the minimum cataractogenic dose of 400 cGy for a fractionated treatment is an underestimate. The exact position of the anterior orbital field margin and thus its distance behind the surface of the eye is also important as regards lens dose. Data from the phantom demonstrate accurately the dose gradient through the eye during standard cranial prophylaxis and may explain the lower incidence of leukaemic relapse in the posterior segment of the eye, and yet explain the persistence of isolated anterior chamber relapses.

Methods of ovarian suppression used in the UK.

Ovarian suppression in the management of breast cancer has had a resurgence in the 1990s. In view of the development of luteinizing hormone-releasing hormone (LHRH) analogues and advances in laparoscopic surgery, we wished to determine whether more consultants are considering these methods for achieving ovarian suppression than radiotherapy. A questionnaire was designed to determine the current practice of consultants in the UK and to discover who is involved in making this decision. It was distributed via the Adjuvant Breast Cancer (ABC) trials office to consultants who enter patients into the ABC premenopausal trial. Seventy-four (72%) questionnaires were analysed. The preferred method of treatment was radiotherapy in 60%, surgery in 30% and LHRH analogues in 9%. Seventy-three per cent of consultants were using more than one technique but did not always involve the patient in the decision-making process to determine which treatment modality to use. Radiotherapy techniques used included using bony landmarks for field borders (46%), using a standard field size (20%) or using ultrasound localization (15%).

Radiotherapy in benign orbital disease. I: Complicated ocular angiomas.

Radiotherapy has been successful in the management of complicated ocular and orbital angiomas, but late morbidity (particularly radiation induced cataract) has been a problem. With modern radiotherapy techniques it is possible to minimise the morbidity to other tissues. By means of a recently developed method of lens-sparing ocular radiotherapy (initially adopted for retinoblastoma therapy) two cases of diffuse ocular haemangioma complicated by retinal detachment have been treated, with evidence of regression.

Cavernous haemangioma presenting as an orbital mass after enucleation for a choroidal melanoma: case report.

A patient presented with an ipsilateral orbital mass four years after enucleation for a choroidal malignant melanoma. Clinical examination revealed a darkly coloured mass suggestive of recurrent melanoma. CT scanning indicated a locally extensive tumour. Management was by excision without resort to orbital exenteration. Pathological examination revealed a cavernous haemangioma. The natural history of this tumour is discussed.

Preoperative topical and intraoperative local mitomycin C adjuvant therapy in the management of ocular surface neoplasias.

AIMS: To demonstrate the efficacy of mitomycin C as adjuvant therapy preoperatively and intraoperatively in the management of recurrent or diffuse ocular surface neoplasias. METHODS: The case notes of 11 patients receiving mitomycin C adjuvant therapy as 0.04% eye drops four times a day in two weekly courses preoperatively and/or a single intraoperative application of 0.4 mg/ml of mitomycin C were reviewed. The histopathology included conjunctival primary acquired melanosis, conjunctival melanomas, sebaceous cell carcinomas with conjunctival intraepithelial spread, and conjunctival intraepithelial squamous neoplasias. Seven patients had additional limited local excision of the residual tumour mass and one had cryotherapy. RESULTS: All cases showed a favourable response to mitomycin C adjuvant therapy with regression in size or retardation of a rapid growth pattern and no serious sequelae. Postoperative follow up of 6-36 months following excision of the lesion with or without intraoperative mitomycin C showed no clinical recurrence in any of the cases. CONCLUSION: In this series, mitomycin C adjuvant therapy of recurrent or diffuse ocular surface neoplasias was well tolerated and showed favourable clinical results.

Radiotherapy in benign orbital disease. II: Ophthalmic Graves' disease and orbital histiocytosis X.

Ophthalmic Graves' disease and histiocytosis X involving the orbit are occasionally refractory to treatment, so that vision may be threatened. In these situations megavoltage external beam radiotherapy should be employed, and the indications for this treatment are discussed. A highly accurate technique is described, using precise planning with information obtained from high definition CT scans, a complete patient head shell for immobilisation, and modern megavoltage radiotherapy treatment machines. As a result the dose to the lens is minimised (to a maximum of 10% of the prescribed dose), and late morbidity will be small. Two cases are described to illustrate this procedure and the response to treatment.

Margin assessment by cavity shaving after breast-conserving surgery: analysis and follow-up of 543 patients.

AIMS: To analyse cavity shaving as a method of assessing completeness of surgical excision after breast-conserving surgery. METHODS: Shavings were taken from the wall of the cavity remaining in the breast after breast-conserving surgery in 543 women. Each shaving was extensively sectioned and the presence and type of microscopic disease recorded. Disease in cavity shavings (tumour bed positivity) was correlated with clinicopathological factors as well as overall survival. RESULTS: Tumour bed positivity (TBP) was found in 37% of patients (16% with invasive disease). Patients were selected for further surgery according to the extent of positivity, which varied widely. A total of 15% of patients underwent re-excision or mastectomy. TBP was significantly associated with high tumour grade, presence of an extensive intraduct component, young age and large tumour diameter. It was also associated with a significantly shorter overall survival when compared to patients who were tumour bed negative. CONCLUSIONS: Cavity shaving is a practical and sensitive method of assessing completeness of excision after breast-conserving surgery. In addition it may provide useful prognostic information.

An iodine-125 plaque for radiotherapy of the eye: manufacture and dosimetric considerations.

A comparison of computer dose calculations and thermoluminescent dosemeter measurements in a phantom is given for an iodine-125 plaque for radiotherapy of the eye. The off-central-axis measurements and their relationship to the central-axis depth doses are documented. It was found that the gold backing of the applicator did not influence dosimetry in the phantom and thus the eye.

Paediatric brachytherapy. I. The role of brachytherapy in the multidisciplinary therapy of localized cancers.

Paediatric brachytherapy is rarely practised but has definite benefit in certain situations. Case reports illustrate the role of current brachytherapy strategies both as radical and salvage procedures and in the multidisciplinary management of childhood cancers.

Periventricular enhancement: a non-pathognomonic sign of intracerebral tumours.

Four cases of periventricular contrast enhancement on computed tomography due to different tumours are reported, emphasizing that periventricular contrast enhancement is a non-specific radiological sign.

Improved external beam radiotherapy for the treatment of retinoblastoma.

An applicator attached to a 6 MV linear accelerator has been adapted to produce a well defined beam for the treatment of retinoblastoma. By using a contact lens as the reference point on the patient's cornea, the beam edge is aligned to just behind the posterior margin of the crystalline lens, thus sparing the anterior chamber and lens from the radiation field. In addition to basic dosimetric measurements made using an ionisation chamber and film densitometry to quantify the output and dose distribution from the applicator, extensive use was made of thermoluminescent dosemeters and a tissue-equivalent anthropomorphic head phantom. This was designed for detailed dosimetry on the eye and was used to confirm the correct positioning and reproducibility of the clinical set-up. We present data that corroborate and extend the dosimetric analyses documented in an earlier Dutch publication. In addition to the improved dosimetric analysis, other advantages include patient immobilisation, anaesthetic procedure and finer couch control as well as a recommendation on the dose prescription.

Extraosseous osteosarcoma of the penis.

Osteosarcomas have been reported as arising in a number of extraosseous primary sites, most commonly in the retroperitoneum and the muscles of the thighs and limb girdles, but also in a variety of other organs. We present a case arising in the penis, which we believe to be only the fifth reported in the literature and the only documented long-term survivor. Careful histopathological analysis and surgical management remain of key importance in the management of all sarcomas arising in soft tissue.

Ulcerative skin reaction from subcutaneous infusion of isotonic methotrimeprazine and diamorphine.

We report an ulcerative skin reaction resulting from a subcutaneous infusion of isotonic methotrimeprazine and diamorphine. Skin reactions are a recognized side effect of this treatment, although they are reduced by the use of the isotonic formulation of methotrimeprazine. Frank ulceration has not been previously reported. It occurred in our patient despite low doses of diamorphine and methotrimeprazine, an isotonic formulation, and a short infusion time.

Restoration of vision by radiotherapy for severe, acute, steroid-refractory, congestive thyroid orbitopathy.

We report the case history of a patient treated with radiotherapy for severe acute thyroid orbitopathy that failed to respond to high-dose corticosteroid therapy. The clinical response to irradiation was rapid, dramatic and sustained after extended follow-up. Although radiotherapy has been used in dysthyroid eye disease, there remains debate over the precise indications for and the timing of its utilization. A review of the literature on the use of radiotherapy for acute thyroid orbitopathy has been undertaken, emphasizing its steroid-sparing potential and its role in avoiding the necessity for surgical orbital decompression.

Ultrasound localization of the ovaries for radiation-induced ovarian ablation.

The case notes and simulator films were reviewed from 70 sequential patients who received pelvic irradiation to induce an early menopause as part of their treatment for breast cancer at the Staffordshire Oncology Centre. These patients underwent ultrasound localization of the ovaries immediately prior to simulation. Altogether, 128 ovaries were plotted on a diagrammatic representation of a gynaecoid pelvis to represent their position in both craniocaudal and lateral dimensions in relation to the true bony pelvis. The craniocaudal ovarian position varied from 2.5 cm above the lower aspect of the sacroiliac joint to 2.0 cm above the symphysis pubis. Three (4.6%) right sided ovaries were within 1 cm medial to the right lateral side wall, with none lying lateral to the wall. Seventeen (26%) left sided ovaries were lying within 1 cm of the left pelvic side wall, with four of these lying outside. The limits of the pelvic fields used were from the top of the sacroiliac joint to the bottom of the symphysis pubis. Sixty-one (88%) upper borders were on or above the lower sacroiliac joint. Twenty-six (38%) and 49 (71%) fields were outside the right and left pelvic side walls respectively. This would suggest that field sizes were larger than standard; however, 87% were smaller than 150 cm(2) (assuming a 10x15-cm field as standard). Only one patient failed to respond to treatment. This was thought to be due to underdosing rather than a geographical miss. This patient was successfully retreated. The authors advocate the use of ultrasound localization prior to planning an irradiation menopause, to ensure that the ovaries are encompassed in the pelvic field, thus preventing a geographical miss and reducing field sizes.

Metastatic breast cancer presenting as Tolosa-Hunt syndrome.

Choroidal involvement is a well-recognized manifestation of metastatic disease, particularly from breast and lung primaries. However, breast cancer can involve other ocular structures. The two patients presented illustrate diffuse orbital involvement of the extraocular muscles, simulating Tolosa-Hunt syndrome. This association has not been reported previously. Both patients responded well to local radiotherapy.

Epirubicin chemotherapy and advanced breast cancer after adjuvant CMF chemotherapy.

There have been conflicting reports on the effect of prior adjuvant chemotherapy on the response of advanced breast cancer to primary chemotherapy. We report a retrospective review of the outcome of chemotherapy with epirubicin 100 mg/m2 for advanced breast cancer in 39 patients who had previously received adjuvant cyclophosphamide, methotrexate and 5-fluorouracil (CMF). The response rate (complete responses plus partial responses) was 38.5%, with a median duration of response of 33 weeks. There was no significant difference in the response rate or duration of survival when these patients were compared with matched controls who had not received adjuvant chemotherapy. However, the limitations of this study were such that an adverse effect of adjuvant CMF on the response to epirubicin cannot be excluded.